Vilsmeier synthesis

Enamines may be reduced by sodium borohydride to give saturated amines, but only if a protonating species is available to convert the enamine initially into the iminium cation (lo). Steroidal g-amino-g,5-dienes are unreactive to sodium boro-hydride alone, but addition of acetic acid leads to rapid reduction via the iminium ion (10) to give gj -amino-A -steroids [224], The possibility that diborane was the reactive species in the NaBHd/HOAc system was excluded by the virtual non-reactivity of the enamine to externally generated diborane. Reduction of the iminium ion derivative (3) of a 6-formyl enol ether has been exploited in a variant of the Vilsmeier synthesis of 6-methyl steroids [22 ], the reduction product was the 6-aminomethyl enol ether (ii) which suffered hydrogenolysis with Raney nickel to give the 6-methylated enol ether (12). 

Aromatic and heterocycHc compounds are formylated by reaction with dialkyl- or alkylarylformamides in the presence of phosphoms oxychloride or phosgene (Vilsmeier aldehyde synthesis) (125). The Vilsmeier reaction is a Friedel-Crafts type formylation (126), since the intermediate cation formed by the interaction of phosphoms oxychloride with formamide is a typical electrophilic reagent. Ionic addition compounds of formamide with phosgene or phosphoms oxychloride are also known (127). 

The Gattermann-Koch reaction when appHed to alkenes or alkanes gives ketones or acids but not aldehydes. However, the Vilsmeier aldehyde synthesis can be appHed to aUphatic compounds. For example, 1,2-diaLkoxyethylenes react with /V-methy1foTmani1ide and POCl to give alkoxymalondialdehydes ... 

Although POCl is the traditional reagent in the Vilsmeier aldehyde synthesis, phosgene may be employed (27—29). 

H- 1-Benzazepine, lV-benzyl-2,3,4,5-tetrahydro-Vilsmeier formylation, 7, 527 IH-l-Benzazepine, 2,3-dihydro-synthesis, 7, 541 IH-l-Benzazepine, 2,5-dihydro-synthesis, 7, 540... 

Benzisothiazole, 3-methyl-bromination, 6, 155 nitration, 6, 154 synthesis, 6, 171, 172 Vilsmeier-Haack reaction, 6, 149, 152... 

Vilsmeier-Haack formylation, 6, 26 Isoxazole-3-thiol, 5-phenyl-reactions, 6, 57 Isoxazolethiols reactions, 6, 57 Isoxazole-3-thiols synthesis, 6, 57, 88 Isoxazole-5-thiols synthesis, 6, 88... 

Vilsmeier-Haack formylation, 4, 222 Pyrrole, 3-acetyl-oxidation, 4, 289 protodeaeetylation, 4, 208 synthesis, 4, 218... 

H,3H- Pyrrolo[l, 2-c]oxazole-l, 3-dione, 5,6,7,8-tetrahydro-IR spectra, 6, 978 [2.2](2,5)Pyrrolophane, N-aryl-rearrangements, 4, 209 Pyrrolophanes natural products, 7, 764 synthesis, 7, 771 Pyrrolophanes, N-aryl-synthesis, 7, 774 (2,4)Pyrrolophanes synthesis, 7, 771 Pyrrolo[3,4-c]pyran-4-ones synthesis, 4, 288 Pyrrolopyrans synthesis, 4, 525, 526 Pyrrolopyrazines synthesis, 4, 526 Pyrrolo[l, 2-a]pyrazines synthesis, 4, 516 Pyrrolo[2,3-6]pyrazines Mannich reaction, 4, 504 Vilsmeier reaction, 4, 505 Pyrrolo[3,4-c]pyrazole, 1,3a,6,6a-tetrahydro-structure, 6, 976 synthesis, 6, 1019 Pyrrolopyrazoles synthesis, 5, 164 Pyrrolo[l,2-6]pyrazoles synthesis, 6, 1002, 1006 Pyrrolo[3,4-c]pyrazoles reactions, 6, 1034 synthesis, 6, 989, 1043 Pyrrolo[3,4-c]pyrazolones synthesis, 6, 989 Pyrfolopyridazines synthesis, 4, 517 Pyrrolo[l, 2-6]pyridazines synthesis, 4, 297 6/7-Pyrrolo[2,3-d]pyridazines synthesis, 4, 291 2/f-Pyrrolo[3,4-d]pyridazines synthesis, 4, 291 6/7-Pyrrolo[3,4-d]pyridazines synthesis, 4, 291... 

Pyrrolo[2,3-d]pyrimidine, 5-cyano-bromination, 4, 506 Pyrrolo[2,3-d]pyrimidine, 5-nitroso-nucleophilic reactions, 4, 507 Pyrrolo[l, 2- c]pyrimidine-3-carboxylic acids methyl ester synthesis, 4, 293 Pyrrolopyrimidine-2,4-diones Mannich reaction, 4, 504 Vilsmeier reaction, 4, 505 Pyrrolopyrimidines synthesis, 4, 514, 517, 524, 527 Pyrrolopyrimidines, chloro-nucleophilic attack, S, 312 Pyrrolo[2,3-d]pyrimidines NMR, 4, 500... 

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